A mid-infrared lab-on-a-chip for dynamic reaction monitoring

Mid-infrared spectroscopy is a sensitive and selective technique for probing molecules in the gas or liquid phase. Investigating chemical reactions in bio-medical applications such as drug production is recently gaining particular interest. However, monitoring dynamic processes in liquids is commonly limited to bulky systems and thus requires time-consuming offline analytics. In this work, we show a next-generation, fully-integrated and robust chip-scale sensor for online measurements of molecule dynamics in a liquid solution. Our fingertip-sized device utilizes quantum cascade technology, combining the emitter, sensing section and detector on a single chip. This enables real-time measurements probing only microliter amounts of analyte in an in situ configuration. We demonstrate time-resolved device operation by analyzing temperature-induced conformational changes of the model protein bovine serum albumin in heavy water. Quantitative measurements reveal excellent performance characteristics in terms of sensor linearity, wide coverage of concentrations, extending from 0.075 mg ml−1 to 92 mg ml−1 and a 55-times higher absorbance than state-of-the-art bulky and offline reference systems.


B. QCLD Device Design
The device fabrication was performed in the in-house state-of-the-art cleanroom facilities ZMNS (Center for micro and nanostructures) at TU Wien. Table 1 shows the QCLD waveguide structure (the detailed AR sequence can be found in [9]).
The implemented DFB grating in the upper cladding further stabilizes the emitted wavelength of the QCL and thus increases the sensitivity of a QCLD-based sensor [10]. This allows the device to address a wider concentration range (<100 µg ml −1 to >90 mg ml −1 ) and distinguish it from laser power fluctuations and occasional modehops. For adequate optical output power of the QCLs, we implemented weakly coupled DFB gratings. Even though leading to broader spectral modes (∼2 cm −1 ), they are still suitable to address the broad absorption features of BSA in D 2 O.

C. QCLD Device Characterization
Supplementary Figure 1: On-chip QCL and QCD characterization. a Comparison of the QCD spectral response (black, dashed) with the spectral emission of Laser 1 around 1597 cm −1 (red) and Laser 2 around 1620 cm −1 (green). Laser tuning measurements at 1597 cm −1 are shown in b (spectra) and d (spectral peak tuning) and at 1620 cm −1 c (spectra), and e (spectral peak tuning) Figure 1(a) shows the detailed analysis of the two lasers at ∼1597 cm −1 and ∼1620 cm −1 and their spectral overlap with the on-chip QCD. In addition, we analyzed the thermally/electrically induced spectral tuning under various laser driving conditions for pulsed operation (pulse length: 100 ns, repetition rate: 5 kHz) in Fig. 1(b) and (c) and observe continuous and mode-hop free tuning, as seen from Fig. 1(d) and (e).

D. Mid-IR Ellipsometry Measurements of PECVD SiN
Supplementary Figure 2: IR Ellipsometry data of PECVD-deposited SiN. Optical constants of the SiN that was used as dielectric-loading layer in the on-chip DLSPP waveguide, measured between 2 µm and 11 µm wavelength.
We performed infrared ellipsometry measurements of SiN deposited with a regular PECVD (plasma enhanced chemical vapor deposition) reactor (Oxford Plasmalab 80 Plus) at 300 • C with the same recipe as for the DL layer of the on-chip DL-SPP waveguides. The values of n and k at the wavelength of interest of λ ∼ 6.17 µm are extracted to be n SiN = 1.79 and k SiN = 0.012.

E. LOD Calculation
We use the standard definition for the LOD: LOD = 3 · std(t) slope −1 [11], where std(t) is the standard deviation of the measured signal during the signal recording time t and the slope is the slope m of the calibration function, as shown in Fig. 3 for the QCLD sensor.

F. Heating Rate of BSA in the Thermal Denaturation Experiment
We compared the heating rates for the three BSA concentrations of 20, 40 and 60 mg ml −1 during the denaturation experiments. Figure 4 shows that the heating rates (expressed as their 1st derivative) are similar for all three concentrations.
Supplementary Figure 4: Heating rates per BSA concentration. Comparison of the 1 st derivative of the heating rate in (°C s −1 ) for the three different BSA concentrations: 20 mg ml −1 (red), 40 mg ml −1 (blue) and 60 mg ml −1 (violet).